J Nephropharmacol. 2014; 3(1): 3–4. http://www.jnephropharmacology.com
NPJ
Journal of Nephropharmacology
Vitamin D therapy in diabetic kidney disease Mahmoud Rafieian-Kopaei1, Hamid Nasri2* Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran
1 2
Article Type:
Epidemiology and Prevention Article History:
Received: 7 August 2013 Accepted: 24 October 2013 ePublished: 1 January 2014
Keywords:
Vitamin D Diabetic nephropathy Renal failure
R
Implication for health policy/practice/research/medical education
Diabetic nephropathy is a major risk of end-stage kidney failure and is associated with greater morbidity and mortality, predominantly with augmented cardiovascular disease. Many complex factors relate to the progression of nephropathy of diabetic patients .Current investigations have focused on the optimization of renin-angiotensin system blockade in patients with diabetic nephropathy using combinations of drugs that target this pathway, however further studies have focused on the potential of new therapies that either target various pathways up-regulated by hyperglycemia or other targets believed to promote progression of diabetic nephropathy.
Please cite this paper as: Rafieian-Kopaei M, Nasri H. Vitamin D therapy in diabetic kidney disease. J Nephropharmacol 2014; 3(1): 3-4.
ecently an article published by Ahmadi et al, entitled “whether vitamin D3 is effective in reducing proteinuria in type 2 diabetic patients? (1). In a randomized double blinded parallel groups clinical trial, 51 diabetic individuals with proven diabetic kidney disease and vitamin D deficiency/ insufficiency and stable hypertension, dyslipidemia, and hyperglycemic treatment were selected. Patients received oral vitamin D3 (pearl 50000 IU) or placebo one pearl every week for 12 weeks. Patients were assessed at baseline and 12 weeks after intervention from the point of 25(OH)D level, and urine albumin/creatinine ration (1). They assessed, plasma 25(OH)D level prior and after the intervention after and urine albumin/ creatinine ratio. In their study, there was not a decrease in proteinuria in patients who obtained vitamin D for a period of 3 months (1). Diabetic nephropathy is a major risk of endstage kidney failure and is associated with greater morbidity and mortality, predominantly with augmented cardiovascular disease (2,3). Many complex factors relate to the progression of diabetic nephropathy (4,5). Current investigations have focused on the optimization of renin-angiotensin system blockade in patients with nephropathy of diabetes using combinations of drugs that target this pathway (6-8), however further studies have focused on the potential of new therapies that either target various pathways up-regulated by hyperglycemia or other targets believed to promote progression of diabetic nephropathy for example the endothelin system, inflammation and vitamin D receptors (9-11). Up to now, various evidence
supports, vitamin D as a negative regulator of the circulating and local tissue renin-angiotensin system, while the reninangiotensin system have a critical role in the physiology of sodium and volume homeostasis (6-11). Excess activity of the renin-angiotensin system is associated with high blood pressure, kidney disease and diabetes. Indeed it is possible that, the most important putative mechanisms associating vitamin D to blood glucose control is its regulation of the reninangiotensin system suppression of renin biosynthesis (2-8). It seems that treatment with vitamin D reduced the urinary urine albumin/creatinine ratio level by suppressing the compensatory renin increase in diabetic nephropathy (2-8). These beneficial consequences might be contributed to suppressed renal expression of renin and transforming growth factor beta (TGF-β) which may or may not be angiotensin II dependent (3-10). Recent studies have shown that low 25(OH)D3 levels are common in individuals with albuminuria. Thus, the antiproteinuric efficacy of vitamin D in diabetic kidney disease is mediated by vitamin D receptor activation (4-11). More recent studies suggests that the effect of vitamin D receptor activation is partly that of negatively regulating renin-angiotensin system, which plays a significant role in the development of diabetic kidney disease (4-11). It is possible that, non-positive result on diminution of proteinuria by vitamin D therapy in the study of Ahmadi et al. may be due to short period of treatment. Also, in their study, it should be better to dissociate males from females and then analyze the data distinctly, while Houng et al.
*Corresponding author: Professor Hamid Nasri, Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran. Tel: +983112208081, Fax: +98311223 5043, E-mail: [email protected]
Epidemiology and Prevention
ARTICLE INFO
Rafieian-Kopaei M et al
found that mean 25(OH)D3 concentrations were meaningfully lower in females than in males (12). In fact, a low vitamin D status was more closely associated with micro-albuminuria in males than in females (2-8,13). Limitations of study conducted by Ahmadi et al, need to be considered too. The sample size was small. In addition, limited duration of exposure to drug, as mentioned. Importantly, the season may affect vitamin D concentrations, and might also influence treatment outcome a factor that is very difficult to control. In addition, the best effective dose needs further exploration and finally, lack of evaluation of parathormone levels, while a bulk of evidences, revealed the positive association of parathyroid hormone and level blood pressure as an aggravating factor for diabetic kidney disease (2-9,12-14). Thus the negative result on reducing the proteinuria in diabetic kidney disease, should not discourage its use. We suggest, more prospective interventional studies with larger duration with control of confounders to better found this aspect of diabetic patients. Authors’ contributions HN and MRK wrote the manuscript equally Conflict of interests The authors declared no competing interests. Ethical considerations Ethical issues (including plagiarism, informed consent, misconduct, double publication and redundancy) have been completely observed by the authors. Funding/Support None declared. References 1. Ahmadi N, Mortazavi M, Iraj B, Askari G. Whether vitamin D3 is effective in reducing proteinuria in type 2 diabetic patients? J Res Med Sci 2013; 18(5): 374-7. 2. Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism 2012; 61(4): 450-8. 3. Rammos G, Tseke P, Ziakka S. Vitamin D, the reninangiotensin system, and insulin resistance. Int Urol
Nephrol 2008; 40: 419-26. 4. Lau T, Carlsson PO, Leung PS. Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetologia 2004; 47: 240-8. 5. Leung PS. Current research of the RAS in diabetes mellitus. Adv Exp Med Biol 2010; 690: 131-53. 6. Van Buren PN, Toto R. Current update in the management of diabetic nephropathy. Curr Diabetes Rev 2013; 9(1): 6277. 7. Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, et al. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem 2007; 282(41): 29821-30. 8. Ohara I, Tanimoto M, Gohda T, Yamazaki T, Hagiwara S, Murakoshi M, et al. Effect of combination therapy with angiotensin receptor blocker and 1,25-dihydroxyvitamin D(3) in type 2 diabetic nephropathy in KK-A(y)/Ta mice. Nephron Exp Nephrol 2011; 117(4): e124-32. 9. de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 2010; 376(9752): 1543-51. 10. Furukawa M, Gohda T, Tanimoto M, Tomino Y. Pathogenesis and novel treatment from the mouse model of type 2 diabetic nephropathy. Scientific World Journal 2013; 2013: 928197. 11. Zhang Z, Sun L, Wang Y, Ning G, Minto AW, Kong J, et al. Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney Int 2008; 73(2): 163-71. 12. Huang Y, Yu H, Lu J, Guo K, Zhang L, Bao Y, et al. Oral supplementation with cholecalciferol 800 IU ameliorates albuminuria in Chinese type 2 diabetic patients with nephropathy. PLoS One 2012; 7(11): e50510. 13. Bonakdaran S, Hami M, HatefiA. The effects of calcitriol on albuminuria in patients with type-2 diabetes mellitus. Saudi J Kidney Dis Transpl 2012; 23(6): 1215-20. 14. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1, 25-DihydroxyVitamin D (3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002; 110: 229-38.
Copyright © 2014 The Author(s); Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
4
Journal of Nephropharmacology, Volume 3, Number 1, January 2014
http://www.jnephropharmacology.com
NPJ
Journal of Nephropharmacology
Vitamin D therapy in diabetic kidney disease Mahmoud Rafieian-Kopaei1, Hamid Nasri2* Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran
1 2
Article Type:
Epidemiology and Prevention Article History:
Received: 7 August 2013 Accepted: 24 October 2013 ePublished: 1 January 2014
Keywords:
Vitamin D Diabetic nephropathy Renal failure
R
Implication for health policy/practice/research/medical education
Diabetic nephropathy is a major risk of end-stage kidney failure and is associated with greater morbidity and mortality, predominantly with augmented cardiovascular disease. Many complex factors relate to the progression of nephropathy of diabetic patients .Current investigations have focused on the optimization of renin-angiotensin system blockade in patients with diabetic nephropathy using combinations of drugs that target this pathway, however further studies have focused on the potential of new therapies that either target various pathways up-regulated by hyperglycemia or other targets believed to promote progression of diabetic nephropathy.
Please cite this paper as: Rafieian-Kopaei M, Nasri H. Vitamin D therapy in diabetic kidney disease. J Nephropharmacol 2014; 3(1): 3-4.
ecently an article published by Ahmadi et al, entitled “whether vitamin D3 is effective in reducing proteinuria in type 2 diabetic patients? (1). In a randomized double blinded parallel groups clinical trial, 51 diabetic individuals with proven diabetic kidney disease and vitamin D deficiency/ insufficiency and stable hypertension, dyslipidemia, and hyperglycemic treatment were selected. Patients received oral vitamin D3 (pearl 50000 IU) or placebo one pearl every week for 12 weeks. Patients were assessed at baseline and 12 weeks after intervention from the point of 25(OH)D level, and urine albumin/creatinine ration (1). They assessed, plasma 25(OH)D level prior and after the intervention after and urine albumin/ creatinine ratio. In their study, there was not a decrease in proteinuria in patients who obtained vitamin D for a period of 3 months (1). Diabetic nephropathy is a major risk of endstage kidney failure and is associated with greater morbidity and mortality, predominantly with augmented cardiovascular disease (2,3). Many complex factors relate to the progression of diabetic nephropathy (4,5). Current investigations have focused on the optimization of renin-angiotensin system blockade in patients with nephropathy of diabetes using combinations of drugs that target this pathway (6-8), however further studies have focused on the potential of new therapies that either target various pathways up-regulated by hyperglycemia or other targets believed to promote progression of diabetic nephropathy for example the endothelin system, inflammation and vitamin D receptors (9-11). Up to now, various evidence
supports, vitamin D as a negative regulator of the circulating and local tissue renin-angiotensin system, while the reninangiotensin system have a critical role in the physiology of sodium and volume homeostasis (6-11). Excess activity of the renin-angiotensin system is associated with high blood pressure, kidney disease and diabetes. Indeed it is possible that, the most important putative mechanisms associating vitamin D to blood glucose control is its regulation of the reninangiotensin system suppression of renin biosynthesis (2-8). It seems that treatment with vitamin D reduced the urinary urine albumin/creatinine ratio level by suppressing the compensatory renin increase in diabetic nephropathy (2-8). These beneficial consequences might be contributed to suppressed renal expression of renin and transforming growth factor beta (TGF-β) which may or may not be angiotensin II dependent (3-10). Recent studies have shown that low 25(OH)D3 levels are common in individuals with albuminuria. Thus, the antiproteinuric efficacy of vitamin D in diabetic kidney disease is mediated by vitamin D receptor activation (4-11). More recent studies suggests that the effect of vitamin D receptor activation is partly that of negatively regulating renin-angiotensin system, which plays a significant role in the development of diabetic kidney disease (4-11). It is possible that, non-positive result on diminution of proteinuria by vitamin D therapy in the study of Ahmadi et al. may be due to short period of treatment. Also, in their study, it should be better to dissociate males from females and then analyze the data distinctly, while Houng et al.
*Corresponding author: Professor Hamid Nasri, Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran. Tel: +983112208081, Fax: +98311223 5043, E-mail: [email protected]
Epidemiology and Prevention
ARTICLE INFO
Rafieian-Kopaei M et al
found that mean 25(OH)D3 concentrations were meaningfully lower in females than in males (12). In fact, a low vitamin D status was more closely associated with micro-albuminuria in males than in females (2-8,13). Limitations of study conducted by Ahmadi et al, need to be considered too. The sample size was small. In addition, limited duration of exposure to drug, as mentioned. Importantly, the season may affect vitamin D concentrations, and might also influence treatment outcome a factor that is very difficult to control. In addition, the best effective dose needs further exploration and finally, lack of evaluation of parathormone levels, while a bulk of evidences, revealed the positive association of parathyroid hormone and level blood pressure as an aggravating factor for diabetic kidney disease (2-9,12-14). Thus the negative result on reducing the proteinuria in diabetic kidney disease, should not discourage its use. We suggest, more prospective interventional studies with larger duration with control of confounders to better found this aspect of diabetic patients. Authors’ contributions HN and MRK wrote the manuscript equally Conflict of interests The authors declared no competing interests. Ethical considerations Ethical issues (including plagiarism, informed consent, misconduct, double publication and redundancy) have been completely observed by the authors. Funding/Support None declared. References 1. Ahmadi N, Mortazavi M, Iraj B, Askari G. Whether vitamin D3 is effective in reducing proteinuria in type 2 diabetic patients? J Res Med Sci 2013; 18(5): 374-7. 2. Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism 2012; 61(4): 450-8. 3. Rammos G, Tseke P, Ziakka S. Vitamin D, the reninangiotensin system, and insulin resistance. Int Urol
Nephrol 2008; 40: 419-26. 4. Lau T, Carlsson PO, Leung PS. Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetologia 2004; 47: 240-8. 5. Leung PS. Current research of the RAS in diabetes mellitus. Adv Exp Med Biol 2010; 690: 131-53. 6. Van Buren PN, Toto R. Current update in the management of diabetic nephropathy. Curr Diabetes Rev 2013; 9(1): 6277. 7. Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, et al. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem 2007; 282(41): 29821-30. 8. Ohara I, Tanimoto M, Gohda T, Yamazaki T, Hagiwara S, Murakoshi M, et al. Effect of combination therapy with angiotensin receptor blocker and 1,25-dihydroxyvitamin D(3) in type 2 diabetic nephropathy in KK-A(y)/Ta mice. Nephron Exp Nephrol 2011; 117(4): e124-32. 9. de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 2010; 376(9752): 1543-51. 10. Furukawa M, Gohda T, Tanimoto M, Tomino Y. Pathogenesis and novel treatment from the mouse model of type 2 diabetic nephropathy. Scientific World Journal 2013; 2013: 928197. 11. Zhang Z, Sun L, Wang Y, Ning G, Minto AW, Kong J, et al. Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney Int 2008; 73(2): 163-71. 12. Huang Y, Yu H, Lu J, Guo K, Zhang L, Bao Y, et al. Oral supplementation with cholecalciferol 800 IU ameliorates albuminuria in Chinese type 2 diabetic patients with nephropathy. PLoS One 2012; 7(11): e50510. 13. Bonakdaran S, Hami M, HatefiA. The effects of calcitriol on albuminuria in patients with type-2 diabetes mellitus. Saudi J Kidney Dis Transpl 2012; 23(6): 1215-20. 14. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1, 25-DihydroxyVitamin D (3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002; 110: 229-38.
Copyright © 2014 The Author(s); Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
4
Journal of Nephropharmacology, Volume 3, Number 1, January 2014
http://www.jnephropharmacology.com
